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Aim:We aimed to assess the effect of a functional polymorphism of CYP3A5 on lumefantrine pharmacokinetics. Patients & methods:Sixty-nine women diagnosed with malaria received standard doses of artemether–lumefantrine. Concentration–time data for lumefantrine and genotyping data were obtained for each participant. Pharmacokinetic-genotype associative relationships were assessed using linear regressions, Mann–Whitney U-test or Kruskal–Wallis statistics. Results:Average age and weight (standard deviation) of the patients were 33 (6.8) years and 59.5 (11.6) kg, respectively. CYP3A5*3 genotype associated with the log-transformed maximum concentration with the median (interquartile range) values of 8279 (6516–13,420) and 6331 (4093–8631) ng/ml (p = 0.032) among the carriers and noncarriers of CYP3A5*3, respectively. Besides, the NR1I3c.152-1089T>C genotypes had an associative trend with the lumefantrine area under the curve (AUC0–96h) and clearance. Conclusion:CYP3A5*3 genetic variant is associated with a high maximum plasma concentration of lumefantrine. This warrants further investigations on the association between CYP3A5*3gene variants, lumefantrine pharmacokinetics and electrophysiological effect.

Background: As per current treatment guidelines, artemether-lumefantrine and efavirenz-based antiretroviral therapy are recommended drugs for falciparum malaria and human immunodeficiency virus (HIV) infections, respectively. A liquid chromatography-ultraviolet detection method for simultaneous quantification of lumefantrine and efavirenz was developed and validated for efficacy and pharmacokinetic clinical studies. Lumefantrine and efavirenz were separated using a 100 × 4.6 mm × 3 µm Fortis C18chromatographic column, and a multistep gradient mobile phase. Calibration curves were obtained with a series of standard solutions containing known concentrations of the chemical reference of both analytes prepared concomitantly in drug-free plasma. The assay was validated within the calibration ranges of 78.125–20,000 ng/mL for lumefantrine and 187.15–24,000 ng/mL for efavirenz. Stability assessment was carried out with or without heating the quality control sample to 58 °C for 45 min. The method was employed to measure the plasma concentrations of lumefantrine and efavirenz in a study conducted among malaria-HIV co-infected patients. Result: Lumefantrine and efavirenz were well separated from each other and from the biological matrix. The method demonstrated a good recovery of 72.64% for lumefantrine and 117.17% for efavirenz. The intra- and inter-day accuracy presented as 95.36–105.14% for lumefantrine and 104.11–115% for efavirenz and precision ranged from 1.15 to 6.45% for lumefantrine and 0.43 to 13.12 for efavirenz, were within ± 15% at the three quality control levels. The analytes from both quality control lots and samples collected from HIV-malaria co-infected individuals were found to be stable post-deactivation of infectious virus by heating to 58 °C for 45 min. Conclusion: The assay is accurate, precise and shown to simultaneously measure the lumefantrine and EFV in human plasma.

There is an increased recognition of the need to identify and quantify the impact of genetic polymorphisms on drug-drug interactions. This study investigated the pharmacogenetics of the pharmacokinetic drug-drug interaction between nevirapine and artemether-lumefantrine in HIV-positive and HIV-negative adult Nigerian subjects.

Artemether-lumefantrine is often coadministered with efavirenz-based antiretroviral therapy for malaria treatment in HIV-infected women during pregnancy. Previous studies showed changes in lumefantrine pharmacokinetics due to interaction with efavirenz in nonpregnant adults.